Polymorphisms within genes encoding Ikaros family proteins IKZF1 and IKZF3 in multiple myeloma patients treated with thalidomide.

Background: Multiple myeloma (MM) is a hematological malignancy characterized by the presence of abnormal plasma cells. It is associated with anemia, bone lesions and renal dysfunction. Immunomodulatory drugs (IMiDs) are commonly used in MM treatment.

Molecular Structure of Paraoxonase-1 and Its Modifications in Relation to Enzyme Activity and Biological Functions-A Comprehensive Review.

PON1 is a Ca-dependent enzyme that indicates a hydrolytic activity towards a broad spectrum of substrates. The mechanism of hydrolysis catalyzed by this enzyme is poorly understood. It was shown that the active site of PON1 is highly dynamic.

Coelimycin inside out - negative feedback regulation by its intracellular precursors.

Coelimycin (CPK) producer Streptomyces coelicolor A3(2) is a well-established model for the genetic studies of bacteria from the genus Streptomyces, renowned for their ability to produce a plethora of antibiotics and other secondary metabolites. Expression regulation of natural product biosynthetic gene clusters (BGCs) is highly complex, involving not only regulatory proteins, like transcription factors, but also the products of the biosynthetic pathway that may act as ligands for some regulators and modulate their activity. Here, we present the evidence that intracellular CPK precursor(s) (preCPK) is involved in a negative feedback loop repressing the CPK BGC.

Multifunctional Indomethacin Conjugates for the Development of Nanosystems Targeting Cancer Treatment.

Purpose: It is well known that the nonsteroidal anti-inflammatory drug (NSAID) indomethacin (IND) exhibits significant anticancer potential reported not only by in vitro and in vivo studies, but also in clinical trials. Despite promising results, IND is not widely used as an adjunctive agent in cancer therapy due to the occurrence of several gastrointestinal side effects, primarily after oral administration. Therefore, this study aimed to develop a nanosystem with reduced toxicity and risk of side effects for the delivery of IND for cancer treatment.

Anhydrous microwave synthesis as efficient method for obtaining model advanced glycation end-products.

Introduction: Advanced glycation end-products (AGEs) are capable of stimulating oxidative stress and inflammation. This study investigates the synthesis of medium crosslinked AGEs (the most optimal form of AGEs because of soluble in water, used in many assays as markers) and their biochemical properties.

Methods: One of model protein-myoglobin from horse heart muscle (MB) and a chosen respective glycation factor - D-melibiose (mel), acrolein (ACR), D-glucose (glc), 4-hydroksynonenal (4HNE), trans-2-nonenal (T2N), methylglyoxal (MGO) - were subjected to high temperature water synthesis (HTWS) and high temperature microwave synthesis in anhydrous conditions (HTMS).

Synthesis, X-ray studies and antiproliferative activity of novel lasalocid amides.

Seeking new drug candidates among compounds of natural origin is an effective and widely used method of fighting various diseases, especially cancer. Lasalocid acid is one of the naturally occurring polyether ionophore antibiotics, which also exhibits interesting anticancer activity. Therefore, to expand the knowledge about the anticancer properties of lasalocid derivatives, a series of its new amides were synthesized and their antiproliferative activity against cancer cell lines was studied.

Comprehensive Approaches to Combatting Biofilms: From Biofilm Structure to Phage-Based Therapies.

-a multidrug-resistant (MDR) pathogen that causes, for example, skin and soft tissue wounds; urinary tract infections; pneumonia; bacteremia; and endocarditis, particularly due to its ability to form robust biofilms-poses a significant challenge in clinical settings. This structure protects the bacteria from immune responses and antibiotic treatments, making infections difficult to eradicate. Given the rise in antibiotic resistance, alternative therapeutic approaches are urgently needed.

Lower limb interosseous membrane in foetuses.

Background: The leg interosseous membrane (LIM) stabilises the tibia and the fibula. These two bones articulate at the proximal and distal tibiofibular joints. In addition, the LIM is the place of attachment of tibialis anterior muscle, extensor digitorum longus muscle, fibularis tertius muscle (anatomical variant), tibialis posterior muscle and flexor hallucis longus muscle.

Site-Specific and Fluorescently Enhanced Installation of Post-Translational Protein Modifications via Bifunctional Biarsenical Linker.

To understand how particular post-translational modifications (PTMs) affect the function of a target protein, it is essential to first prepare and investigate the target with the modification at the desired position. This drives the continuous development of site-specific protein modification technologies. Here, we present the chemical synthesis and application of the biarsenical linker SrtCrAsH-EDT, which has a dual labeling functionality.

Gb3 trisaccharide-bearing exosomes as a novel neutralizer for Shiga toxin type 1.

Shiga toxin types 1 (Stx1) and 2 (Stx2), produced by Shiga toxin-producing Escherichia coli (STEC) and Shigella dysenteriae, are key virulence factors responsible for severe foodborne diseases, such as hemorrhagic colitis and hemolytic uremic syndrome (HUS). The receptors for Stxs are Gb3 and P1 glycotope, which contain the Galα1→4Gal epitope and are synthesized by human α1,4-galactosyltransferase (A4galt). Stx-related infections pose a global public health challenge, owing to the limited therapeutic options due to the restricted use of antibiotics.

The association between maternal stress and human milk concentrations of cortisol and prolactin.

Psychosocial stress affects the relationship between prolactin (PRL) and cortisol (CORT). The dynamics of PRL and CORT changes under stress in human milk (HM) are largely unknown. We investigated how maternal stress related to recent life changes affects milk CORT and PRL concentrations.

Selective and complementary antimicrobial and antiviral activity of silver, copper, and selenium nanoparticle suspensions in deep eutectic solvent.

Metallic and nonmetallic nanoparticles are bioactive compounds that exhibit broad resistance to bacteria, fungi, and even viruses. In this paper, a deep eutectic solvent (DES) based on betaine, glucose, and ethylene glycol was used to obtain suspensions of silver, copper, and selenium nanoparticles. Depending on the nanoparticle precursor used, Ag, Cu, and Se nanoparticles (NPs) with an average particle size of 50-100 nm were prepared, and the properties of the products were confirmed by the STEM, XPS, DLS, and UV-VIS methods.

Local and systemic humoral immune responses to Histophilus somni recombinant antigens administered intranasally and subcutaneously to dairy calves.

Bovine respiratory disease (BRD) causes significant economic losses in dairy calves. Induction of an early immune response via parenteral vaccination is complicated by the interference of colostral immunity. In this study, we investigated early immunization against selected conserved bacterial antigens.

Polymorphic Variants in the Vitamin D Receptor and Clinical Parameters of Rheumatoid Arthritis Patients Undergoing Anti-TNF Treatment.

Vitamin D levels have been related to the severity and progression of various autoimmune disorders. In this study, we aimed to investigate the impact of genetic variability in the vitamin D receptor (VDR) gene on disease susceptibility and progression in patients with rheumatoid arthritis (RA) treated with tumor necrosis factor (TNF) inhibitors. The study comprises 121 RA patients subjected to anti-TNF therapy genotyped for four VDR polymorphic variants: rs1544410 (I), rs2228570 (I), rs731236 (I), and rs7975232 (I).

Neutrophil Elastase, Neuron-Specific Enolase, and S100B Protein as Potential Markers of Long-Term Complications Caused by COVID-19 in Patients with Type 2 Diabetes Mellitus (T2DM) and Advanced Stage of Diabetic Nephropathy (NfT2DM)-Observational Studies.

Despite numerous studies conducted by various research teams, predicting long-term outcomes (known as Post-COVID-19 Syndrome, PCS) that may result from Coronavirus Disease 2019 (COVID-19) remains challenging. PCS affects over a million people, primarily those with comorbid conditions. Therefore, it is crucial to undertake research aimed at developing a predictive model for early diagnosis of PCS, which in turn would enable faster preventive actions.

Association of Genetic Variants at the and Loci Encoding p27 and Cyclin D2 Cell Cycle Regulators with Susceptibility and Clinical Course of Chronic Lymphocytic Leukemia.

Beyond the essential role of p27 and cyclin D2 in cell cycle progression, they are also shown to confer an anti-apoptotic function in peripheral blood (PB) lymphocytes. Although the aberrant longevity and expression of p27 and cyclin D2 in leukemic cells is well documented, the exact mechanisms responsible for this phenomenon have yet to be elucidated. This study was undertaken to determine the associations between polymorphisms in the and genes (encoding p27 and cyclin D2, respectively) and susceptibility to chronic lymphocytic leukemia (CLL), as well as their influence on the expression of both cell cycle regulators in PB leukemic B cells and non-malignant T cells from untreated CLL patients divided according to the genetic determinants studied.

Modifications in the C-terminal tail of TrkC significantly alter neurotrophin-3-promoted outgrowth of neurite-like processes from PC12 cells.

TrkB and TrkC are quite common neurotrophin receptors found on the same cells in CNS. In the C-terminal tail, TrkB and TrkC differ only in two amino acid residues at positions immediately preceding the tyrosine residue, which, upon phosphorylation, becomes the docking site for phospholipase Cγ1 (PLCγ1). The question arose whether such a difference near the PLCγ1 docking site might contribute to differential response to neurotrophin.

Synergistic Proliferation Effects of Xanthohumol and Niflumic Acid on Merkel and Glioblastoma Cancer Cells: Role of Cell Membrane Interactions.

The objective of our research was to determine the effects of xanthohumol (XN), a flavonoid isolated from hops (), and the anti-inflammatory drug niflumic acid (NA), separately and in combination with each other, on the proliferation of human cancer cells. Additionally, so as to understand the mechanism underlying the anticancer properties of the tested compounds, their effects on the biophysical parameters of a model membrane were assessed. The cells were incubated with XN and NA at various concentrations, either individually or in combination with each other.

Emerging Paradigms in Cancer Metastasis: Ghost Mitochondria, Vasculogenic Mimicry, and Polyploid Giant Cancer Cells.

The capacity of cancer cells to migrate from a primary tumor, disseminate throughout the body, and eventually establish secondary tumors is a fundamental aspect of metastasis. A detailed understanding of the cellular and molecular mechanisms underpinning this multifaceted process would facilitate the rational development of therapies aimed at treating metastatic disease. Although various hypotheses and models have been proposed, no single concept fully explains the mechanism of metastasis or integrates all observations and experimental findings.

Outer membrane protein C is a protective and unique vaccine antigen against Shigella flexneri 3a.

The anti-Shigella vaccine is one of the WHO's top priorities. Every year the disease kills more than 200,000 people worldwide and poses a serious threat to children under 5 years of age and the elderly. Increasing antibiotic resistance and limitations in diagnostics emphasize the need to develop an effective vaccine.

The contribution of neutrophils to bacteriophage clearance and pharmacokinetics in vivo.

With the increasing prevalence of antimicrobial-resistant bacterial infections, there is interest in using bacteriophages (phages) to treat such infections. However, the factors that govern bacteriophage pharmacokinetics in vivo remain poorly understood. Here, we have examined the contribution of neutrophils, the most abundant phagocytes in the body, to the pharmacokinetics of i.